p21cip1/waf1, is an important intermediate by which p53 mediates its role as an inhibitor of cellular proliferation in response to DNA damage. p21cip1/waf1 may bind to and inhibit cyclin-dependent kinase activity, preventing the phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression, and thus proliferation. Induction or overexpression of p21cip1/waf1 leads to cell cycle inhibition and growth suppression in cells.
In many cells, p21cip1/waf1 is increased in response to different types of stress, such as oxidative stress, x-ray radiation, and DNA damage. Oxidative stress is reported to be associated with numerous diseases and conditions, including stroke, hypoxia, ischemia, spinal cord injury and neurodegenerative conditions. Accordingly, compounds that enhance the expression of p21cip1/waf1 and methods of identifying such compounds are beneficial for treating conditions and diseases that can be treated by enhancing expression of p21cip1/waf1 or by inhibiting cell cycle progression.